Genomic Study Points to Natural Origin of COVID-19
Posted on by Dr. Francis Collins
No matter where you go online these days, there’s bound to be discussion of coronavirus disease 2019 (COVID-19). Some folks are even making outrageous claims that the new coronavirus causing the pandemic was engineered in a lab and deliberately released to make people sick. A new study debunks such claims by providing scientific evidence that this novel coronavirus arose naturally.
The reassuring findings are the result of genomic analyses conducted by an international research team, partly supported by NIH. In their study in the journal Nature Medicine, Kristian Andersen, Scripps Research Institute, La Jolla, CA; Robert Garry, Tulane University School of Medicine, New Orleans; and their colleagues used sophisticated bioinformatic tools to compare publicly available genomic data from several coronaviruses, including the new one that causes COVID-19.
The researchers began by homing in on the parts of the coronavirus genomes that encode the spike proteins that give this family of viruses their distinctive crown-like appearance. (By the way, “corona” is Latin for “crown.”) All coronaviruses rely on spike proteins to infect other cells. But, over time, each coronavirus has fashioned these proteins a little differently, and the evolutionary clues about these modifications are spelled out in their genomes.
The genomic data of the new coronavirus responsible for COVID-19 show that its spike protein contains some unique adaptations. One of these adaptations provides special ability of this coronavirus to bind to a specific protein on human cells called angiotensin converting enzyme (ACE2). A related coronavirus that causes severe acute respiratory syndrome (SARS) in humans also seeks out ACE2.
Existing computer models predicted that the new coronavirus would not bind to ACE2 as well as the SARS virus. However, to their surprise, the researchers found that the spike protein of the new coronavirus actually bound far better than computer predictions, likely because of natural selection on ACE2 that enabled the virus to take advantage of a previously unidentified alternate binding site. Researchers said this provides strong evidence that that new virus was not the product of purposeful manipulation in a lab. In fact, any bioengineer trying to design a coronavirus that threatened human health probably would never have chosen this particular conformation for a spike protein.
The researchers went on to analyze genomic data related to the overall molecular structure, or backbone, of the new coronavirus. Their analysis showed that the backbone of the new coronavirus’s genome most closely resembles that of a bat coronavirus discovered after the COVID-19 pandemic began. However, the region that binds ACE2 resembles a novel virus found in pangolins, a strange-looking animal sometimes called a scaly anteater. This provides additional evidence that the coronavirus that causes COVID-19 almost certainly originated in nature. If the new coronavirus had been manufactured in a lab, scientists most likely would have used the backbones of coronaviruses already known to cause serious diseases in humans.
So, what is the natural origin of the novel coronavirus responsible for the COVID-19 pandemic? The researchers don’t yet have a precise answer. But they do offer two possible scenarios.
In the first scenario, as the new coronavirus evolved in its natural hosts, possibly bats or pangolins, its spike proteins mutated to bind to molecules similar in structure to the human ACE2 protein, thereby enabling it to infect human cells. This scenario seems to fit other recent outbreaks of coronavirus-caused disease in humans, such as SARS, which arose from cat-like civets; and Middle East respiratory syndrome (MERS), which arose from camels.
The second scenario is that the new coronavirus crossed from animals into humans before it became capable of causing human disease. Then, as a result of gradual evolutionary changes over years or perhaps decades, the virus eventually gained the ability to spread from human-to-human and cause serious, often life-threatening disease.
Either way, this study leaves little room to refute a natural origin for COVID-19. And that’s a good thing because it helps us keep focused on what really matters: observing good hygiene, practicing social distancing, and supporting the efforts of all the dedicated health-care professionals and researchers who are working so hard to address this major public health challenge.
Finally, next time you come across something about COVID-19 online that disturbs or puzzles you, I suggest going to FEMA’s new Coronavirus Rumor Control web site. It may not have all the answers to your questions, but it’s definitely a step in the right direction in helping to distinguish rumors from facts.
 The proximal origin of SARS-CoV-2. Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF. Nat Med, 17 March 2020. [Epub ahead of publication]
Coronavirus (COVID-19) (NIH)
COVID-19, MERS & SARS (National Institute of Allergy and Infectious Diseases/NIH)
Andersen Lab (Scripps Research Institute, La Jolla, CA)
Robert Garry (Tulane University School of Medicine, New Orleans)
Coronavirus Rumor Control (FEMA)
NIH Support: National Institute of Allergy and Infectious Diseases; National Human Genome Research Institute
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Posted In: News
Tags: ACE2, bats, bioengineering, camels, civets, coronavirus, Coronavirus Rumor Control, COVID-19, evolutionary biology, FEMA, genomics, man-made, MERS, natural, natural origin, new coronavirus, pandemic, pangolin, SARS, SARS-CoV-2, social distancing, spike protein, viral pandemics, virology
Very informative. Thanks for this post.
Excellent results and analysis. Should be propagated positively in the scientific world round the globe.
Thanks for this interesting analysis. Rumour machines seem to always suggest malign intention/ambitions. However, a non-natural (ie engineered virus) does not have to have maliganed intention associated with it.
I am not a virologist or a pulmonary specialist, With that caveat in mind, perhaps this was ‘just’ a research project to evaluate the role of ‘spike proteins’ and their ACE2 binding ability in infectivity cross-species? It just happened that it all went wrong. Let me explain.
Suppose researches hypothesised that by mutating certain parts of the SPIKE protein, this would reduce binding to ACE2 and infectivity of the virus. Suppose they generated these mutatnt viruses based on the sequence of the known ‘bat virus’. As there was thought to be little binding of the mutant virus to ACE2, no or little, precuation was taken when handling the mutant virus.. But bang comes an unexpected infectivity! This is accompanied by retention of binding to ACE2 and serendipitiously, and unfortunately, the mutant virus has unraveled a new binding site to ACE2. Thise in the field of corona viruses are best placed to critique this, and I would be very interested to hear views.
So basically, a negative control virus (ie a virus that wasn’t supposed to bind ACE2) was being designed but turned out to still bind ACE2 and retain infectivity. No malicious intention by any country – just chance and experiment that went wrong!
A job well done, I like Genetic Engineering
Thank you for keeping us informed.
Great information, seems we may be able to deduce a new generation of blood pressure medications via the newly identified alternate binding site.
Ummm, UAMS researchers conducted a study, which was published which included a dendrogram, showing the bat origination. Where is their credit?
Always learn from your posts😊
I admit most of your posts are too scientific for most people – but this one I really appreciate because there are so many people putting out videos and posts on Facebook of so much false conspiracy theories that this should help put a stop to some of them on my timeline. THANK YOU & GOD BLESS YOU FOR THE WORK YOU DO
Maybe address this cleanliness with people who deal with animals on a routine basis too. Including those house pets luxuries.
Fascinating – thanks for sharing this summary. I’ve been looking at viral mutation of DNA caused by fragments of viral codes and HERVs (HERV-L, -K, W, Fc). Any thoughts regarding whether this might have a role in this multi specie mutation of human genome?
first big mistake… facebook is only a rumor mill for weak minded individuals who believe all that is read there. Always said find your own answers. Ty for the information.
Just what we needed to know. Great article.
I appreciate very much for efforts of your group to evidence the way of origin of COVID-19.It is important to defence the honour of our work as scientists also . Congratulations by full heart. Prof of Clinical Genetics Alina Midro from Poland Białystok
Bats and pangolins belong in a zoo not a fish market. I think often of allergies and how the body reacts and try to relate it to science. With the protein and cells binding, trouble breathing, chest pain, and coughing seems like a allergic response of some kind.
Does the binding of the spike protein to the Ace2 receptor protein suggest that ACE2 inhibitors by competitive inhibition could prevent the binding of the corona virus to its target ????
A big applause to Dr. Collins, Director NIH, USA for providing a crisp update about the emrging global pandemic Coronavirus Disease 2019 (Covid-19); the expert snapshots including take-home message has been elegantly presented for borth the scientific and clinical community for propeling long-term, patient-friendly, safe, cost-effective public health oriented clinically significant research in the coming years so as to successfully diminish the increasing morbidity/mortality trends amongst at-risk COVID-19 susceptible populations of varying genetic landscapes worldwide!
The protein-spike structure of the vius, replication, transmission, etc. have been meticulously presented with due credit to the scientists at Scripps/Tulane, USA for providing novel research outputs in the Covid-19 research field; I would like to add that pooled population-clinical samples with adherence to core tenets of good practic research with collaborative scientific integrity, may be randomly collected by Covid-19 researchers including Covid-19 symptomatic cases and age-/gender-/ethnicity-matched healthy volunteers from random populations as disease-free controls, for precisely dissecting the susceptibility, virulence, relapse, recurrence and mortality after exposure to the Covid-19. Pharmacogenetics/genomics studies would be immensely beneficial in identifying early vs advanced stage Covid-19 positive patients’ morbidity/mortality trends, and therapeutic targeting of biochemical/metabolic pathways including the Angiotensin-II (ACE-2) and interrelated receptor/cell-death signaling cascades especiall Toll-like receptors, Autophagy, Apotosis, High-mobility groupbox-1, cytokine/interferon-gamma signaling, etc. may aid in rationale design of predictive biomarkers for Covid-19 susceptible populations of both American, Italian, Asian: Chinese, Indian (North as well as South Indian), Australian, Danish, African, German, British, etc, cohorts.
Psychosocial interventions with physician-patient counseling sessions including post-screening awareness talks for practising self-isolation/quarantining, social distancing, etc, may be performed for dimininshing perceived social stigma, behavioral/coping problems, financial instablity, etc. in Covid-19 positive cases of genetically heterogeneous population-subsets with differential lifestyles and cultural backgrounds.
Overall, there are still few myths regarding the “deadly Covid-19” spreading its “spiky-tentacles” worldwide, and therefore, I strongly feel the urgency of timeline-based cost-effective global public health research model-development by public health experts/policy-leaders including my American expert colleagues, for battling the pandemic; moreover, the Government-issued country-wide state-wide shut-downs to effectively eradicate the growing morbidity/mortality and person-to-person transmission of Covid-19 deserves an applause. My homecountry India in the Asia-Pacific region recently issued a 21-day shut-down for cost-effectively and successfully battling the Covid-19 pandemic with stringent policy-based issues.
Adequate surveillance protocols should be stringently defined by the experts for large-scale implementation to successfully and stringently overcome the Covid-19 scare in USA, India and other affected nations.
My sincere “Get well soon” wishes to Covid-19 positive American, Indian and globally-affected populations……..it has been aptly said thet prevention is better than cure………………and in this context, we should stringently adhere to the preventive measures mandated by the Government(s) including social distancing and effective quaranting to eventually overcome the deadly Covid-19 and emerge victorious after winning the Covid-19 battle on a global field!
Can we block binding sites in human cells or vice versa so virus cannot attack or attach?
Who doubts that to test both their own as well as the Wests capacity to.respond, that the Cinese govt wouldn’t release on their own people for world wide propogation a natural deadly cv-10 pathogen?
Research their blueprint for asymetric warfare against the West. Mao had no hesitation in murdering a million good Chinese citizens to attain his Great Leap Forward. Know Your Enemy!!
You say “Existing computer models predicted that the new coronavirus would not bind to ACE2 as well as the SARS virus. However, to their surprise, the researchers found that the spike protein of the new coronavirus actually bound far better than computer predictions, likely because of natural selection on ACE2 that enabled the virus to take advantage of a previously unidentified alternate binding site. Researchers said this provides strong evidence that that new virus was not the product of purposeful manipulation in a lab. In fact, any bioengineer trying to design a coronavirus that threatened human health probably would never have chosen this particular conformation for a spike protein.”
There is a logical mistake done here: absence of evidence is not evidence of absence. Additionally, how can you ensure that an bioengineer will follow prescribed logical rules suposed by you. Indeed, computer models are always updated to include new or better models. otherwise you just become stucked on old solutions.
Very strange. The paper in question actually comes nowhere near “proving” that the virus is a product purely a result of natural evolution, and to even claim that it does at this point is intellectually deeply dishonest.
Firstly, the authors note that the ACE2 binding solution that SARS-CoV-2 uses is found nowhere else in nature. While they claim this *proves* a fully natural origin for SARS-CoV-2, even a moment’s thought reveals this as a glaring non-sequitur. Something never before seen in nature is probably *more* likely to be unnatural, not less.
Second, the authors note that the virus has no clear ancestor, but rather consists of parts related to two quite different viruses that inhabit different animals. This too is claimed to prove a natural origin for SARS-CoV-2, yet again it is a non-sequitur: in fact it makes the natural creation of such a virus more implausible.
Thus in both cases, I would argue that a fully natural origin is if anything made *less* likely by the facts in the paper. That some of the most prestigious scientists in the world are loath to entertain any possible role of laboratory constructs or genetic engineering in the pedigree of SARS-CoV-2, given its numerous genomic peculiarities, is a sign that genuine inquiry has departed and self-interested sophistry is now in charge.
I totally agree with your well written comment. I also had the same doubts and questions when reading this paper, and came to the same conclusions as you. The reason I read this paper was to see if there is any credible proof that SARS-CoV-2 originated in nature, but this paper convinces me that there still is no such proof. Quite the opposite, I am more convinced that it was not naturally created. So now suspicion falls on the authors of such papers, and their motivations.
“Firstly, the authors note that the ACE2 binding solution that SARS-CoV-2 uses is found nowhere else in nature. (…) Second, the authors note that the virus has no clear ancestor, but rather consists of parts related to two quite different viruses that inhabit different animals (…)”
In the article above, Mr. Collins mentions:
“A related coronavirus that causes severe acute respiratory syndrome (SARS) in humans also seeks out ACE2.”
This appears to be explained respectively described in more detail at https://www.niaid.nih.gov/news-events/nih-study-shows-how-mers-coronavirus-evolves-infect-different-species. It was published about one and a half years ago:
“Evidence suggests that both viruses originated in bats before transmitting to civets and camels, respectively. (…) To cause infection, a virus must first attach to a receptor molecule on cells of the host species. This interaction is highly dependent on the shape of the receptors, which the host genes control. To evaluate how MERS-CoV evolves to infect host cells, the scientists tested 16 bat species and found that the virus could not efficiently enter cells with receptors from the common vampire bat, Desmodus rotundus. They then grew virus on cells that had vampire bat receptors and observed the virus evolving to better infect the cells. After a few generations, the virus had completely adapted to the vampire bat receptor. By studying how the shape of MERS-CoV changed over time to attach to the new host receptor, the scientists found similarities with prior studies of SARS-CoV. Thus, while these two viruses are different, they use the same general approach to enter the cells of new species.”
(Referencing “Adaptive evolution of MERS-CoV to species variation in DPP4”, available at http://doi.org/10.1016/j.celrep.2018.07.045.)
Dear Doctor Collins, interesting article on COVID-19, However Dr. Einstein had a different opinion on the topic and if I am correct considered it to be the first of three such virus events coming from a biological weapons laboratory North of the European Gothic line circa year 1940, later known  as the green line
I’m thrilled to gain an enormous knowledge regarding covid-19 from an academia source and with passed knowledge of some my college bio courses, I am able to understand the science behind this article. It makes me sick when I sit somewhere and hear people come up with conspiracy theories that do not add up and any science behind it. NIH always a great source for those eager to learn about science and health.